Summary:engraftment after high-dose chemotherapy compared to autologous BM. Allogeneic transplants with PBSC have also been shown to provide hastened tri-lineage Growth factor administration to donors prior to bone marrow (BM) harvesting results in an enrichment of the engraftment. 1,2 However, there is a growing concern that unmanipulated allogeneic PBSC transplants may lead to a graft for myeloid precursors. In animals, growth factorprimed BM has a higher repopulating ability than higher incidence of graft-versus-host disease (GVHD) especially of chronic extensive GVHD. 3 Intriguingly, the untreated BM. Ten patients received an HLA-identical sibling, allogeneic transplant using granulocyte colonyincidence of GVHD after allogeneic PBSC transplantation seems not to correlate with the number of T lymphocytes stimulating factor (G-CSF)-stimulated BM. Stimulation consisted of G-CSF at 10 g/kg/day for 2 days prior to infused. 3 Furthermore, positive CD34 + cell selection of PBSC with concurrent depletion of T lymphocytes does not harvest. Patients were transplanted for various benign and malignant hematological conditions. The GVHD seem sufficient to eliminate GVHD. Whether the G-CSF PBSC mobilization schedules currently in use result in simultaneous enrichengraftment of white cells and platelets. On average they attained an ANC of у1 ؋10 9 /l 9 days earlier and ment of the stem cell and progenitor content of the BM, or simply in a shift of these cells from the BM to the peria platelet count of у20 ؋ 10 9 /l 6 days earlier than historical controls receiving unstimulated HLA-identical pheral blood, has not been elucidated. A small number of studies has been conducted to detersibling BM. Hospitalization was shortened by a mean of 10 days and transfusion requirements were modest. mine the progenitor content and engraftment capability of growth factor-stimulated BM. In mice, G-CSF and stem None of the patients developed severe GVHD or disease relapse. Two patients died of severe VOD post-BMT cell factor produce 10-fold or greater increase in the BM repopulating ability in competitive assays. 10 In human studand thus were unevaluable for platelet engraftment. A third patient died of TTP on day 76 post-BMT. Seven ies, an increased number of committed myeloid progenitors 11 and CD34 + cells 12 were documented in BM harvests patients are alive and well 49-585 days post-BMT. Stimulated BM may provide a valuable alternative to from stimulated donors. Two studies using interleukin-3 and G-CSF 13 or GM-CSF 14 -stimulated BM failed to show allogeneic BM and PBSC transplants. Ideal stimulation regimens need to be investigated.faster engraftment compared to unstimulated BM but a third study using G-CSF showed hastened engraftment.
One hundred fifty-one cases of patients who underwent proctectomy for inflammatory bowel disease at the Lahey Clinic were analyzed with respect to the factors that predispose to delay in perineal wound healing. Significantly poorer healing took place in patients with Crohn's colitis, in men with ulcerative colitis, and in patients with ulcerative colitis who underwent one-stage operations. Factors that were not statistically significant but that appeared to contribute to delay in healing were younger age of patients and presence of anal fistula. A comparison is made with the results of other series, and recommendations for treatment and prevention are presented.
Nonmyeloablative allogeneic peripheral blood progenitor cell transplantation with low-dose total body irradiation (TBI; 200 cGy) plus fludarabine followed by cyclosporine and mycophenolate mofetil results in modest graft rejection rates. Acute and chronic graft-versus-host diseases (GVHD) are also seen and may not differ substantially from those that occur after fully ablative transplantation. Adding antithymocyte globulin (ATG) to pretransplant conditioning produces substantial immunosuppression. Because of its persistence in the circulation, ATG can achieve in vivo T-cell depletion. Twenty-five patients who were not eligible for conventional fully ablative allogeneic stem cell transplantation by virtue of age or comorbidities underwent nonmyeloablative allogeneic transplantation with ATG 15 mg/kg/d days -4 to -1, TBI 200 cGy on a single fraction on day -5, and fludarabine 30 mg/m(2)/d on days -4 to -2. Oral mycophenolate mofetil 15 mg/kg every 12 hours and cyclosporine 6 mg/kg every 12 hours were started on day -5. Grafts were unmanipulated peripheral blood progenitor cells mobilized with filgrastim 10 microg/kg/d and collected on day 5. The median age of the recipients was 57 years (range, 30-67 years); diagnoses were non-Hodgkin lymphoma (n = 11), acute myeloid leukemia (n = 6), multiple myeloma (n = 3), acute lymphoblastic leukemia (n = 2), severe aplastic anemia (n = 1), paroxysmal nocturnal hemoglobinuria (n = 1), and myelodysplastic syndrome (n = 1). The median CD34(+) and CD3(+) contents of the grafts were 7.6 x 10(6)/kg and 1.6 x 10(8)/kg, respectively. Five patients received voluntary unrelated donor grafts. Three patients, 2 with voluntary unrelated donor grafts and 1 with a sib donor, received a 1 antigen-mismatched graft. The rest were fully matched. Twenty-two of 25 patients were evaluable for chimerism. Sixteen had >/=95% donor chimerism. Four patients displayed 80% to 90% donor chimerism, 1 displayed 78%, and 1 displayed 64%. Eleven patients relapsed with their original disease. One patient rejected the graft at 180 days. The median hospital stay was 27 days. Complications included GVHD in 6 patients (3 patients had grade I or II GVHD of skin and liver, and 3 patients had grade III or IV GVHD of liver and gut). Two of the patients with GVHD had mismatched grafts. Transplant-related toxicity was seen in 4 patients and infection in 5 patients. The median length of follow-up was 162 days (range, 17-854 days). Complete remissions were seen in 10 patients. Four patients remained in complete response (CR) at 280 to 595 days. One patient relapsed with non-Hodgkin lymphoma after a CR of 728 days. Of the 25 patients, 16 died (6 of relapsed disease, 4 of GVHD, 3 of infection, and 3 of transplant-related toxicity) and 9 are alive (6 with CR-2 of them after donor leukocyte infusion-and 3 with relapsed disease). The addition of ATG to low-dose TBI and fludarabine nonmyeloablative conditioning was well tolerated and resulted in >80% donor engraftment in this small cohort. As in other series of truly nonmyeloab...
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